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Understanding universal aspects of quantum dynamics is an unresolved problem in statistical mechanics. In particular, the spin dynamics of the one-dimensional Heisenberg model were conjectured as to belong to the Kardar-Parisi-Zhang (KPZ) universality class based on the scaling of the infinite-temperature spin-spin correlation function. In a chain of 46 superconducting qubits, we studied the probability distribution of the magnetization transferred across the chain's center, [Formula: see text]. The first two moments of [Formula: see text] show superdiffusive behavior, a hallmark of KPZ universality. However, the third and fourth moments ruled out the KPZ conjecture and allow for evaluating other theories. Our results highlight the importance of studying higher moments in determining dynamic universality classes and provide insights into universal behavior in quantum systems.
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Haloperidol is currently used in addictology for the treatment of acute psychotic disorders, including acute alcoholic hallucinosis. The use of haloperidol is often accompanied by the occurrence of adverse drug reactions (ADRs). There is evidence that CYP2D6 isoenzyme is involved in the biotransformation of haloperidol. Aim: The study aimed to evaluate the relationship of 1846G > A polymorphism of the CYP2D6 gene to the equilibrium concentration levels of haloperidol in patients with acute alcoholic hallucinosis. Material and Methods: The study was conducted on 100 male patients with acute alcoholic hallucinosis (mean age 41.4 ± 14.4 years). The efficacy profile was evaluated using the PANSS (Positive and Negative Syndrome Scale) scale. The safety of therapy was assessed using the UKU Side-Effect Rating Scale and the SAS (Simpson-Angus Scale for Extrapyramidal Symptoms) scale. Genotyping was performed using the real-time polymerase chain reaction (Real-time PCR). Equilibrium plasma concentration levels of haloperidol were investigated using the high-performance liquid chromatography with mass spectrometry (HPLC with MS/MS). Results: No statistically significant results were obtained during the therapy efficacy assessment (dynamics of the PANSS score: GG genotype (-13.00 [-16.00; -16.00; -11.00]), GA genotype (-15.00 [-16.75; -13.00], p = 0.728). There was a statistically significant difference in safety assessment scores (dynamics of the UKU score: GG genotype (8.00 [7.00; 10.00]), GA genotype (15.00 [9.25; 18.00], p < 0.001); dynamics of the SAS score: GG genotype (11.00 [9.00; 14.00]), GA genotype (14.50 [12.00; 18.00], p < 0.001). The pharmacokinetic study results showed a statistically significant difference: GG (3.13 [2.32; 3.95]), GA (3.89 [2.92; 5.26], p = 0.010). Thus, a study conducted on a group of 100 patients with acute alcoholic hallucinosis demonstrated an association between the 1846G > A polymorphism of the CYP2D6 gene (rs3892097) and the safety profile of haloperidol therapy. We also revealed the presence of statistically significant difference in the equilibrium concentration levels of haloperidol in patients with the GG and AG genotypes. Conclusion: It can be concluded that patients with the GA genotype have a higher risk of ADRs compared to patients carrying the GG genotype. It is shown that 1846G > A polymorphism of the CYP2D6 gene (rs3892097) has a statistically significant effect on the equilibrium concentration levels of haloperidol.
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Delirio por Abstinencia Alcohólica , Antipsicóticos , Trastornos Psicóticos , Adulto , Humanos , Masculino , Persona de Mediana Edad , Delirio por Abstinencia Alcohólica/tratamiento farmacológico , Antipsicóticos/farmacocinética , Antipsicóticos/uso terapéutico , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Genotipo , Haloperidol/efectos adversos , Haloperidol/farmacocinética , Haloperidol/uso terapéutico , Trastornos Psicóticos/tratamiento farmacológico , Espectrometría de Masas en TándemRESUMEN
To date, haloperidol has been widely used to treat patients with acute alcoholic hallucinosis. There is strong evidence that haloperidol therapy is commonly associated with adverse drug reactions (ADRs). The 392A > G polymorphism of the CYP3A4*1B gene (rs2740574) is known to affect the metabolism rates of haloperidol; hence it correlates with both therapy efficacy and safety parameters. Objective: The study objective was to investigate the effect of 392A > G polymorphism of the CYP3A4*1B gene (rs2740574) on the efficacy and safety profiles of haloperidol in patients with acute alcoholic hallucinosis. Methods: This study enrolled 100 male patients suffering from acute alcoholic hallucinosis (mean age 41.4 ± 14.4 years). The efficacy profile of haloperidol was assessed using the PANSS (Positive and Negative Syndrome Scale) validated psychometric scale. The safety profile of therapy was assessed with the UKU Side-Effect Rating Scale and the SAS (Simpson-Angus Scale for Extrapyramidal Symptoms) scale. Genotyping was performed using the real-time polymerase chain reaction (Real-time PCR). Results: There were no statistically significant results for the efficacy rates (dynamics of the PANSS score: AA genotype -14.00 [-16.00; -12.00], AG genotype -13.00 [-14.00; -10.50], p = 0.306). Similarly, there was no statistically significant difference in the safety profiles (dynamics of the UKU score: AA genotype - 9.00 [7.00; 13.00], AG genotype - 8.50 [7.25; 10.50], p = 0.620; dynamics of the SAS score: AA genotype -12.00 [10.00; 16.75], AG genotype - 10.00 [10.00; 12.25], p = 0.321). Conclusion: The study demonstrated that the 392A > G polymorphism of the CYP3A4*1B gene (rs2740574) in patients with acute alcoholic hallucinosis does not affect the efficacy and safety rates of haloperidol therapy.
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Antipsicóticos , Haloperidol , Adulto , Humanos , Masculino , Persona de Mediana Edad , Antipsicóticos/efectos adversos , Antipsicóticos/uso terapéutico , Citocromo P-450 CYP3A/genética , Genotipo , Haloperidol/efectos adversos , Haloperidol/uso terapéutico , Polimorfismo de Nucleótido SimpleRESUMEN
Systems of correlated particles appear in many fields of modern science and represent some of the most intractable computational problems in nature. The computational challenge in these systems arises when interactions become comparable to other energy scales, which makes the state of each particle depend on all other particles1. The lack of general solutions for the three-body problem and acceptable theory for strongly correlated electrons shows that our understanding of correlated systems fades when the particle number or the interaction strength increases. One of the hallmarks of interacting systems is the formation of multiparticle bound states2-9. Here we develop a high-fidelity parameterizable fSim gate and implement the periodic quantum circuit of the spin-½ XXZ model in a ring of 24 superconducting qubits. We study the propagation of these excitations and observe their bound nature for up to five photons. We devise a phase-sensitive method for constructing the few-body spectrum of the bound states and extract their pseudo-charge by introducing a synthetic flux. By introducing interactions between the ring and additional qubits, we observe an unexpected resilience of the bound states to integrability breaking. This finding goes against the idea that bound states in non-integrable systems are unstable when their energies overlap with the continuum spectrum. Our work provides experimental evidence for bound states of interacting photons and discovers their stability beyond the integrability limit.
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Introduction: Escitalopram is commonly prescribed to patients with recurrent depressive disorder. Some of them do not show adequate response to treatment with escitalopram, while many of them experience adverse drug reactions. Objective: The objective of our study was to evaluate the impact of -806C>T polymorphism of CYP2C19 (CYP2C19*17) on the concentration/dose ratio of escitalopram in patients with recurrent depressive disorder. Material and methods: Our study enrolled 267 patients with recurrent depressive disorder (average age -40.2 ± 16.4 years). Treatment regimen included escitalopram in an average daily dose of 12.5 ± 5.0 mg per day. The efficacy and safety rates of treatment were evaluated using the international psychometric scales. For genotyping, we performed the real-time polymerase chain reaction. Therapeutic drug monitoring has been performed using HPLC-MS/MS. Results: Our findings revealed the statistically significant results in terms of both treatment efficacy evaluation (HAMD scores at the end of the treatment course): (CC) 9.0 [7.0; 11.0], (CT) 4.0 [2.0; 6.0] and (TT) 2.0 [1.0; 4.0], p < 0.001; and safety profile (the UKU scores): (CC) 7.0 [7.0; 8.0], (CT) 3.0 [3.0; 4.0] and (TT) 3.0 [2.0; 3.0], p < 0.001. We revealed no statistically significant results for the concentration/dose ratio of escitalopram in patients with different genotypes: (CC) 5.762 [3.939; 9.076], (CT) 5.714 [3.485; 8.533] and (TT) 7.388 [4.618; 10.167], p = 0.268). Conclusion: The CYP2C19*17 genetic variant significantly affected the efficacy and safety profiles of escitalopram in a group of 267 patients with recurrent depressive disorder but did not greatly affect its equilibrium plasma concentration.
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Citalopram , Trastorno Depresivo , Citalopram/efectos adversos , Citocromo P-450 CYP2C19/genética , Trastorno Depresivo/tratamiento farmacológico , Escitalopram , Humanos , Polimorfismo Genético , Espectrometría de Masas en TándemRESUMEN
Polar Rashba-type semiconductor BiTeI doped with magnetic elements constitutes one of the most promising platforms for the future development of spintronics and quantum computing thanks to the combination of strong spin-orbit coupling and internal ferromagnetic ordering. The latter originates from magnetic impurities and is able to open an energy gap at the Kramers point (KP gap) of the Rashba bands. In the current work using angle-resolved photoemission spectroscopy (ARPES) we show that the KP gap depends non-monotonically on the doping level in case of V-doped BiTeI. We observe that the gap increases with V concentration until it reaches 3% and then starts to mitigate. Moreover, we find that the saturation magnetisation of samples under applied magnetic field studied by superconducting quantum interference device (SQUID) magnetometer has a similar behaviour with the doping level. Theoretical analysis shows that the non-monotonic behavior can be explained by the increase of antiferromagnetic coupled atoms of magnetic impurity above a certain doping level. This leads to the reduction of the total magnetic moment in the domains and thus to the mitigation of the KP gap as observed in the experiment. These findings provide further insight in the creation of internal magnetic ordering and consequent KP gap opening in magnetically-doped Rashba-type semiconductors.
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Introduction: Phenazepam is commonly administered to patients diagnosed with major depressive disorder. Some proportion of such patients do not show adequate response to treatment regimen containing phenazepam, whereas many of them experience type A adverse drug reactions. Previous studies showed that CYP2D6 IS involved in the biotransformation of phenazepam, the activity of which is highly dependent on the polymorphism of the gene encoding it. Objective. The objective of the study was to evaluate the impact of 1846G>A polymorphism of the CYP2D6 gene on the concentration/dose indicator of phenazepam, using findings on enzymatic activity of CYP2D6 (as evaluated by the 6M-THBC/pinoline ratio measurement) and on CYP2D6 expression level obtained by measuring the hsa-miR-370-3p plasma concentration levels in patients suffering from major depressive disorder. Material and methods: The study enrolled 191 patients with recurrent depressive disorder (age -40.0 ± 16.3 years). Treatment regimen included phenazepam in an average daily dose of 6.0 ± 2.3 mg per day. Treatment efficacy was assessed using the validated psychometric scales. Therapy safety was assessed using the UKU Side-Effect Rating Scale. For genotyping and estimation of the microRNA (miRNA) plasma levels we performed the real-time polymerase chain reaction (PCR Real-time). The activity of CYP2D6 was evaluated using the HPLC-MS/MS method by the content of the endogenous substrate of given isoenzyme and its metabolite in urine (6M-THBC/pinoline). Therapeutic drug monitoring has been performed using HPLC-MS/MS. Results: Our findings didn't reveal the statistically significant results in terms of the treatment efficacy evaluation (HAMA scores at the end of the treatment course): (GG) 6.0 [4.0; 8.0] and (GA) 6.0 [5.0; 7.8], p > 0.999; the statistical significance in the safety profile was not obtained (the UKU scores): (GG) 3.0 [2.0; 4.0] and (GA) 3.0 [3.0; 3.0], p > 0.999. We didn't reveal a statistical significance for concentration/dose indicator of phenazepam in patients with different genotypes: (GG) 0.812 [0.558; 1.348] and (GA) 0.931 [0.630; 1.271], p = 0.645). Analysis of the results of the pharmacotranscriptomic part of the study didn't show the statistically significant difference in the hsa-miR-370-3p plasma levels in patients with different genotypes: (GG) 22.5 [16.9; 29.8], (GA) 22.7 [15.7; 31.5], p = 0.695. At the same time, correlation analysis didn't reveal a statistically significant relationship between the phenazepam efficacy profile evaluated by changes in HAMA scale scores and the hsa-miR-370-3p plasma concentration: rs = -0.01, p = 0.866. Also, we didn't reveal the correlation between the miRNA concentration and safety profile: rs = 0.07, p = 0.348. Also we did not reveal the relationship between the CYP2D6 enzymatic activity (as evaluated by 6M-THBC/pinoline ratio measurement) and the hsa-miR-370-3p plasma concentration: rs = -0.14, p = 0.056. At the same time, correlation analysis did not reveal a statistically significant relationship between the phenazepam concentration and the hsa-miR-370-3p plasma concentration: rs = -0.05, p = 0.468. Conclusion: The effect of genetic polymorphism of the CYP2D6 gene on the efficacy and safety profiles of phenazepam was not demonstrated in a group of 191 patients with recurrent depressive disorder. At the same time, hsa-miR-370-3p does not remain a promising biomarker for assessing the level of CYP2D6 expression, because it does not correlate with encoded isoenzyme activity.
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Benzodiazepinas/farmacocinética , Citocromo P-450 CYP2D6/sangre , Trastorno Depresivo Mayor , MicroARNs/genética , Citocromo P-450 CYP2D6/genética , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/genética , Humanos , Espectrometría de Masas en TándemRESUMEN
Quantum computing can become scalable through error correction, but logical error rates only decrease with system size when physical errors are sufficiently uncorrelated. During computation, unused high energy levels of the qubits can become excited, creating leakage states that are long-lived and mobile. Particularly for superconducting transmon qubits, this leakage opens a path to errors that are correlated in space and time. Here, we report a reset protocol that returns a qubit to the ground state from all relevant higher level states. We test its performance with the bit-flip stabilizer code, a simplified version of the surface code for quantum error correction. We investigate the accumulation and dynamics of leakage during error correction. Using this protocol, we find lower rates of logical errors and an improved scaling and stability of error suppression with increasing qubit number. This demonstration provides a key step on the path towards scalable quantum computing.
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Citalopram is commonly prescribed to patients suffering from major depressive disorder. Some of them do not respond adequately to therapy with citalopram, while many of them experience type A adverse drug reactions. Current research revealed that CYP2C19 isoenzyme is involved in the biotransformation of citalopram. The objective of our study was to investigate the impact of 681G>A polymorphism of the CYP2C19 gene on the efficacy, safety and the concentration/dose indicator of citalopram. Our study enrolled 130 patients with major depressive disorder and comorbid alcohol use disorder (average age-38.7 ± 14.1 years). Therapy regimen included citalopram in an average daily dose of 31.1 ± 14.4 mg per week. Therapy efficacy and safety were evaluated using the international psychometric scales. For genotyping, we performed the real-time polymerase chain reaction. Our findings revealed the statistically significant results in terms of the treatment efficacy evaluation (HAMD scores at the end of the treatment course): (GG) 8.0 [8.0; 9.0] and (GA) 10.0 [9.0; 11.0], p < 0.001. In the safety profile (the UKU scores), the statistical significance was also obtained: (GG) 3.0 [3.0; 4.0] and (GA) 5.0 [4.0; 5.0], p < 0.001. We revealed a statistical significance for concentration/dose indicator of citalopram in patients with different genotypes: (GG) 2.543 [1.659; 4.239] and (GA) 4.196 [2.643; 5.753], p < 0.001). The effect of CYP2C19 genetic polymorphism on the efficacy and safety profiles of citalopram was demonstrated in a group of 130 patients with major depressive disorder.
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Citalopram/uso terapéutico , Citocromo P-450 CYP2C19/genética , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/genética , Polimorfismo Genético/genética , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Adulto , Genotipo , Humanos , MasculinoRESUMEN
Ecdysterone (Ecdy) is a hormone found in arthropods, which regulates their development. It is also synthesized by a number of plants to combat insect pests. It provides a number of beneficial pharmacological effects including the anabolic and adaptogenic ones. Ecdysterone is widely marketed as food supplement to enhance the physical performance of athletes. In addition to the estrogen receptor beta (ERbeta)-dependent anabolic effect of Ecdy in muscles, the molecular mechanisms of the plethora of other Ecdy-induced pharmacological effects remain unknown. The aim of this study was to investigate the pharmacological effect of ecdysterone on human breast cancer cell lines of different molecular subtypes. Surprisingly, in contrast to the anabolic effect on muscle tissues, we have revealed a tumor suppressive effect of Ecdy on a panel of breast cancer cell lines studied. Using the SeaHorse-based energy profiling, we have demonstrated that Ecdy dampened glycolysis and respiration, as well as greatly reduced the metabolic potential of triple negative breast cancer cell lines. Furthermore, we have revealed that Ecdy strongly induced autophagy. As part of the combined treatment, based on the Combination Index (CI) and Dose Reduction Index (DRI), Ecdy synergized with doxorubicin to induce cell death in several breast cancer cell lines. In contrast, Ecdy had only minor effect on non-transformed human fibroblasts. Collectively, our results indicate that ecdysterone can be considered as a new potential adjuvant for genotoxic therapy in treatment of breast cancer patients.
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Quantum algorithms offer a dramatic speedup for computational problems in material science and chemistry. However, any near-term realizations of these algorithms will need to be optimized to fit within the finite resources offered by existing noisy hardware. Here, taking advantage of the adjustable coupling of gmon qubits, we demonstrate a continuous two-qubit gate set that can provide a threefold reduction in circuit depth as compared to a standard decomposition. We implement two gate families: an imaginary swap-like (iSWAP-like) gate to attain an arbitrary swap angle, θ, and a controlled-phase gate that generates an arbitrary conditional phase, Ï. Using one of each of these gates, we can perform an arbitrary two-qubit gate within the excitation-preserving subspace allowing for a complete implementation of the so-called Fermionic simulation (fSim) gate set. We benchmark the fidelity of the iSWAP-like and controlled-phase gate families as well as 525 other fSim gates spread evenly across the entire fSim(θ,Ï) parameter space, achieving a purity-limited average two-qubit Pauli error of 3.8×10^{-3} per fSim gate.
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In the standard model of particle physics, the weak interaction is described by vector and axial-vector couplings only. Nonzero scalar or tensor interactions would imply an additional contribution to the differential decay rate of the neutron, the Fierz interference term. We derive a limit on this hypothetical term from a measurement using spin-polarized neutrons. This method is statistically less sensitive than the determination from the spectral shape but features much cleaner systematics. We obtain a limit of b=0.017(21) at 68.27% C.L., improving the previous best limit from neutron decay by a factor of four.
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A combined study of local structural, electric and ferroelectric properties of SrTiO[Formula: see text]/La[Formula: see text]Sr[Formula: see text]MnO[Formula: see text]/BaTiO[Formula: see text] heterostructures was performed by Piezoresponse Force Microscopy, tunneling Atomic Force Microscopy and Scanning Tunneling Microscopy in the temperature range 30-295 K. The direct correlation of film structure (epitaxial, nanocrystalline or polycrystalline) with local electric and ferroelectric properties was observed. For polycrystalline ferroelectric films the predominant polarization state is defined by the peculiarity of screening the built-in field by positively charged point defects. Based on Scanning Tunneling Spectroscopy results, it was found that a sequent voltage application provokes the modification of local resistive properties related to the redistribution of point defects in thin ferroelectric films. A qualitative analysis of acquired Piezoresponse Force Microscopy, tunneling Atomic Force Microscopy and Scanning Tunneling Microscopy images together with Scanning Tunneling Spectroscopy measurements enabled us to conclude that in the presence of structural defects the competing processes of electron injection, trap filling and the drift of positively charged point defects drives the change of resistive properties of thin films under applied electric field. In this paper, we propose a new approach based on Scanning Tunneling Microscopy/Spectroscopy under ultrahigh vacuum conditions to clarify the influence of point defects on local resistive properties of nanometer-thick ferroelectric films.
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Alprazolam is used in the treatment of patients with anxiety disorders comorbid with alcohol use disorder. Some proportion of these patients does not respond adequately to treatment with alprazolam, while many of them experience dose-dependent adverse drug reactions. Results of the previous studies have shown that CYP3A is involved in the biotransformation of alprazolam, the activity of which is dependent, inter alia, on the polymorphism of the encoding gene. OBJECTIVE: The objective of our study was to investigate the effect of 99366316G>A polymorphism of the CYP3A4 gene on the concentration/dose indicator of alprazolam in patients with anxiety disorders comorbid with alcohol use disorder, using findings on enzymatic activity of CYP3A (as evaluated by the 6-beta-hydroxy-cortisol/cortisol ratio measurement) and on CYP3A4 expression level obtained by measuring the miR-27b plasma concentration levels in patients with anxiety disorders comorbid with alcoholism. MATERIAL AND METHODS: Our study enrolled 105 patients with anxiety disorders comorbid with alcohol use disorder (age - 37.8±14.6 years). Therapy included alprazolam in an average daily dose of 5.6±2.4 mg per day. Treatment efficacy was evaluated using the psychometric scales. Therapy safety was assessed using the UKU Side-Effect Rating Scale. For genotyping and estimation of the microRNA (miRNA) plasma levels, we performed the real-time polymerase chain reaction. The activity of CYP3A was evaluated using the HPLC-MS/MS method by the content of the endogenous substrate of the given isoenzyme and its metabolite in urine (6- beta-hydroxy-cortisol/cortisol). Therapeutic drug monitoring (TDM) has been performed using HPLC-MS/MS. RESULTS: Our study revealed the statistically significant results in terms of the treatment efficacy evaluation (HAMA scores at the end of the treatment course): (GG) 3.0 [2.0; 5.0] and (GA) 4.0 [4.0; 5.0], p = 0.007; at the same time, the statistical significance in the safety profile was not obtained (the UKU scores): (GG) 3.0 [2.0; 3.8] and (GA) 3.0 [1.5; 4.0], p = 0.650. We revealed a statistical significance for concentration/dose indicator of alprazolam in patients with different genotypes: (GG) 1.583 [0.941; 2.301] and (GA) 2.888 [2.305; 4.394], p = 0.001). Analysis of the results of the pharmacotranscriptomic part of the study didn't show the statistically significant difference in the miR-27b plasma levels in patients with different genotypes: (GG) 25.6 [20.4; 28.8], (GA) 25.7 [19.7; 33.1], p = 0.423. At the same time, correlation analysis revealed a statistically significant relationship between the alprazolam efficacy profile evaluated by changes in HAMA scale scores and the miR-27b plasma concentration: rs = 0.20, p = 0.042. Also, we didn't reveal the correlation between the miRNA concentration and safety profile: rs = 0.15, p = 0.127. In addition, we revealed the relationship between the CYP3A enzymatic activity (as evaluated by 6-beta-hydroxycortisol/ cortisol ratio measurement) and the miR-27b plasma concentration: rs = -0.27, p = 0.006. At the same time, correlation analysis revealed a statistically significant relationship between the alprazolam concentration and the miR-27b plasma concentration: rs = 0.28, p = 0.003. CONCLUSION: The effect of genetic polymorphism of the CYP3A4 gene on the efficacy and safety profiles of alprazolam was demonstrated in a group of 105 patients with anxiety disorders comorbid with alcohol use disorder. At the same time, miR-27b remains a promising biomarker for assessing the level of CYP3A4 expression, because it correlates with the encoded isoenzyme's activity.
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Alcoholismo/tratamiento farmacológico , Alprazolam/farmacocinética , Trastornos de Ansiedad/tratamiento farmacológico , Citocromo P-450 CYP3A/genética , MicroARNs/sangre , Polimorfismo Genético/genética , Adulto , Alprazolam/sangre , Biomarcadores/sangre , Biotransformación , Comorbilidad , Citocromo P-450 CYP3A/sangre , Genotipo , Humanos , Isoenzimas , Masculino , MicroARNs/genética , Persona de Mediana Edad , Farmacogenética , Medicina de Precisión , Resultado del Tratamiento , Adulto JovenRESUMEN
HYPOTHESIS: Colloidal cubic silica shells, prepared from cuprous oxide cubes, with a typical size of 100 nm are promising model particles for scattering studies on dilute, as well as concentrated fluids, of non-spherical colloids. EXPERIMENTS: Small angle X-ray scattering, and static light scattering are employed to determine form factors of cubic silica shells and silica covered cuprous oxide cubes. Contrast variation experiments are performed to assess the refractive index and optical homogeneity of the cubic silica shells, which is important for the extension of the scattering study to concentrated dispersions of cubic shells in Part II (Dekker, submitted for publication). RESULTS: The experimental form factors, which compare well to theoretical form factors, manifest cubic silica shells that are dispersed as single stable colloids with a shape intermediate between a sphere and a perfect cube. Contrast variation demonstrates that the silica shells are optically homogeneous, with a refractive index that is independent of the shell thickness. The results presented here open up the possibility to extract structure factors from light scattering measurements on concentrated cube dispersions in Part II.
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We demonstrate diabatic two-qubit gates with Pauli error rates down to 4.3(2)×10^{-3} in as fast as 18 ns using frequency-tunable superconducting qubits. This is achieved by synchronizing the entangling parameters with minima in the leakage channel. The synchronization shows a landscape in gate parameter space that agrees with model predictions and facilitates robust tune-up. We test both iswap-like and cphase gates with cross-entropy benchmarking. The presented approach can be extended to multibody operations as well.
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BACKGROUND: The aim was to estimate the prevalence of harmful alcohol use in relation to socio-demographic characteristics among acutely ill medical patients, and examine identification measures of alcohol use, including the alcohol biomarker phosphatidylethanol 16:0/18:1 (PEth). METHODS: A cross-sectional study, lasting one year at one hospital in Oslo, Norway and one in Moscow, Russia recruiting acute medically ill patients (≥ 18 years), able to give informed consent. Self-reported data on socio-demographics, mental distress (Symptom Check List-5), alcohol use (Alcohol Use Disorder Identification Test-4 (AUDIT-4) and alcohol consumption past 24â¯h were collected. PEth and alcohol concentration were measured in whole blood. RESULTS: Of 5883 participating patients, 19.2% in Moscow and 21.1% in Oslo were harmful alcohol users, measured by AUDIT-4, while the prevalence of PEth-positive patients was lower: 11.4% in Oslo, 14.3% in Moscow. Men in Moscow were more likely to be harmful users by AUDIT-4 and PEth compared to men in Oslo, except of those being ≥ 71 years. Women in Oslo were more likely to be harmful users compared to those in Moscow by AUDIT-4, but not by PEth for those aged < 61 years. CONCLUSIONS: The prevalence of harmful alcohol use was high at both study sites. The prevalence of harmful alcohol use was lower when assessed by PEth compared to AUDIT-4. Thus, self-reporting was the most sensitive measure in revealing harmful alcohol use among all groups except for women in Moscow. Hence, screening and identification with objective biomarkers and self-reporting might be a method for early intervention.
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Alcoholismo/sangre , Alcoholismo/epidemiología , Glicerofosfolípidos/sangre , Hospitalización/tendencias , Adolescente , Adulto , Anciano , Consumo de Bebidas Alcohólicas/sangre , Consumo de Bebidas Alcohólicas/epidemiología , Alcoholismo/diagnóstico , Biomarcadores/sangre , Estudios Transversales , Intervención Educativa Precoz/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Moscú/epidemiología , Noruega/epidemiología , Autoinforme , Adulto JovenRESUMEN
Among polarizers based on the neutron reflection from Super-Mirrors (SMs), solid-state neutron-optical devices have many advantages. The most relevant is the 5-10 times smaller size along the neutron beam direction compared to more traditional air-gap devices. An important condition for a good SM polarizer is the matching of the substrate SLD (Scattering Length Density) with the SM coating SLD for the spin-down component. For traditional Fe/Si SM on the Si substrate, this SLD step is positive when a neutron goes from the substrate to the SM, which leads to a significant degradation of the polarizer performance in the small Q region. This can be solved by replacing single-crystal Si substrates by single-crystal sapphire or quartz substrates. The latter shows a negative SLD step for the spin-down neutron polarization component at the interface with Fe and, therefore, avoid the total reflection regime in the small Q region. In order to optimize the polarizer performance, we formulate the concept of sapphire V-bender. We perform ray-tracing simulations of sapphire V-bender, compare results with those for traditional C-bender on Si, and study experimentally V-bender prototypes with different substrates. Our results show that the choice of substrate material, polarizer geometry, as well the strength and quality of magnetizing field have dramatic effect on the polarizer performance. In particular, we compare the performance of polarizer for the applied magnetic field strength of 50 mT and 300 mT. Only the large field strength (300 mT) provides an excellent agreement between the simulated and measured polarization values. For the double-reflection configuration, a record polarization >0.999 was obtained in the neutron wavelength band of 0.3-1.2 nm with only 1% decrease at 2 nm. Without any collimation, the polarization averaged over the full outgoing capture spectrum, 0.997, was found to be equal to the value obtained previously using only a double polarizer in the "crossed" (X-SM) geometry. These results are applied in a full-scale polarizer for the PF1B instrument.
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Chimeric antigen receptor-modified T-cell therapy (CAR-T therapy) is one of the fastest developing areas of immuno-oncology. Over the past decade, it has revolutionized the cell therapy modality and expedited its pace of development, from optimization of the structure of chimeric antigen receptors and animal model experiments to successful clinical application. The initial designs of the CAR configuration focused on increasing T-cell activation, cytotoxicity, and persistence. However, the first attempts to treat patients with CAR T cells have demonstrated the need for increased safety and controlled activation of genetically modified T cells. Herein, we summarize the different molecular approaches to engineering chimeric antigen receptors for reducing the potential clinical risks of T-cell therapy.